beta-aminoalkanesulfonamide and process therefor



United States Patent 3,235,593 ,B-AMINOALKANESULFONAMIDE AND PROCESS THEREFOR William S. Friediander, Hudson, Wis., 'assignor to Minnesota Mining and Manufacturing Company, St.

Paul, Minn., a corporation of Delaware No Drawing. Filed Oct. 2, 1962, Ser. No. 227,694 3 Claims. (Cl. 260556) This application is a continuation-in-part of my application Serial Number 794,842, now abandoned.

The present invention relates to processes for the preparation of aminoalkanesulfonamides.

So far as can be determined, no method has heretofore been available for the production of alkane sulfonic acids or amides having lateral amino groups, i.e., attached to a non-terminal carbon atom.

It is a principal object of the present invention to provide a process for the preparation of alkanesulfonamides possessing lateral amino groups in the beta position. Additional objects will be apparent from the specification which follows.

In accordance with the above and other objects of the present invention it has been found that alkanesulfonamides possessing lateral amino groups in the beta position can be obtained easily and in good yield by processes employing as starting materials therefor beta-chloroalkanesulfonyl fluorides represented by the formula:

wherein R is hydrogen or an alkyl radical containing not more than about 16 carbon atoms and R' is an alkyl radical containing not more than about 16 carbon atoms. Such products are conveniently termed beta-aminoalkanesulfonamides, but it is to be clearly understood that in the compounds of the present invention the amino group is positioned laterally or secondary, and not terminally. The process for producing the compounds of the present invention may be conveniently accomplished in either one or two steps. In the one step process the beta-chloroalkane sulfonyl fluoride is reacted directly with a stoichiometric amount of ammonia as shown in the following equation:

This reaction may also be accomplished in two steps as represented by the following equations:

(III) In the above equations R and R have the same significance as previously defined and X is a non-protonic base such as tertiary amine, sodium carbonate or any other basic material which is free from reactive hydrogen atoms. It is one of the remarkable features of the present invention that the activity of the beta-position is so high that 3,235,593 Patented Feb. 15, 1966 amino groups can be introduced thereon either by re placement of a chlorine atom or by addition to a double bond. This is apparently a peculiarity of the hydrocarbon sulfonyl fluorides which is here noted for the first time. Although the compounds of the present invention are produced by either process, the one step process comprising heating a beta-chloroalkanesulfonyl fluoride with ammonia is the preferred process since it is more direct and convenient and avoids isolation of the intermediate alkene sulfonyl fluorides. When the alkene sulfonyl fluorides are desired they are readily formed by the reaction of Equation II above.

It will be understood that the term alkyl radical and the noun alkyl have identically the same meaning and significance as used herein and that when an alkyl is stated to be of 1 to 12 carbon atoms it is meant that it has from 1 to 12 carbon atoms and the necessary number of hydrogen atoms.

In carrying out the preferred process of the present invention, the one-step reaction of the beta-chloroalkanesulfonyl fluoride with ammonia is best eflected under pressure in a vessel which is inert to the reactants. Thus, for example, the reactants are charged directly to a glass lined or stainless steel reaction vessel. Charging at a low tem perature serves to minimize volatilization of the reactants. If desired, an inert solvent such as benzene, toluene, hexane, tetralin or xylene may be charged along with the reactants. The reaction vessel, purged of air and sealed, is then heated for a time suflicient to effect reaction. The pressure varies between about 1 and about atmospheres depending upon the temperature of reaction selected and is substantially the autogenous pressure. In general, temperatures may vary from about 0 to about 200 C. or higher. A temperature in the range of about 70 to about C. appears to be particularly suited since excessive pressures requiring special equipment and excessively slow or possibly incomplete reactions are thus avoided.

The first or dehydrochlorination step of the two-step process of the present invention takes place easily and results in excellent yields of the unsaturated compounds. It may be carried out over the wide range of temperatures and in the presence of non-polar solvents described above. It is usually best carried out at lower temperatures and pressures in glass-lined or stainless steel equipment. The reaction is exothermic and is conveniently carried out at moderate, controlled temperatures, i.e. in the range of from about 20 to 100 C. Conveniently the betachloroalkanesulfonyl fluoride is added to a refluxing solution of the non-protonic base in the non-polar solvent, the rate of addition being just suflicient to maintain reflux. After completion of the reaction, the solid hydrochloride is removed and the product alkenesulfonyl fluoride is recovered from the filtrate. The alkenesulfonyl fluorides are useful raw materials in the direct fluorination process described and claimed by Brice and Trott in the U.S. Patent Number 2,732,398.

Reaction of the alkenesulfonyl fluoride with amonia to form the beta-amino-alkene sulfonamide takes place under much the same conditions of temperature, etc. as does the reaction of the beta-chloroalkanesulfonyl fluoride with ammonia to form the beta-aminoallcanesulfonamide. In this instance it is found that a longer period of reaction may be desirable. The ammonium fluoride formed is removed and is substantially free from ammonium chloride.

Illustrative examples of the beta-chloroalkane and alk-l-ene sulfonyl fluorides useful in the process of the invention are: beta-chloropropanesulfonyl fluoride; betachlorobntanesulfonyl fluoride; beta chlorohexanesulfonyl fluoride; beta-chlorooctanesulfonyl fluoride; beta-chlorododecanesulfonyl fluoride; beta-chlorotetradecanesulfonyl fluoride; beta-chlorooctadecanesulfonyl fluoride; betachloro-beta-methyl-propanesulfonyl fluoride (i.e. betachloroisobutanesulfonyl fluoride); beta methyl betachlorobutanesulfonyl fluoride; beta-methyl beta chloropentanesulfonyl fluoride; beta-ethyl beta-chlorobutanesul- 'fonyl fluoride, Z-methyl prop-I-enesulfonyl fluoride, butl-enesulfonyl fluoride, oct-l-enesulfonyl fluoride, dec-lenesulfonyl fluoride, octadec-l-enesulfonyl fluoride, and the like.

The beta-chloroalkanesulfonyl fluoride intermediates are conveniently prepared by adding sulfuryl chlorofluoride to a A-alkene under free radical conditions.

The process and compositions of this invention are now more specifically illustrated by the following detailed examples which are included by way of showing the best mode contemplated of practicing the invention. In these examples all parts are by weight.

Example 1 Ten parts (0.0435 mole) of beta-chlorooctanesulfonyl fluoride and 5 parts (0.294 mole) of liquid ammonia are placed in a heavy-walled glass vessel such as an ampoule which is then chilled in liquid air, evacuated and sealed. The vessel is placed in a rocking type agitator and is agitated for about 40 hours, during which time it is held at about 90 C. At the end of this reaction time the vesse] is removed from the agitator and is found to contain both liquid and solid material. The vessel is cooled and opened and the volatile material is allowed to escape. The non-volatile residue consists of ammonium fluoride, ammonium chloride and solid, crude beta-aminooctanesulfonamide, which may be represented by the formula:

This residue is extracted with diethyl ether in a Soxhlet apparatus and the beta-aminooctanesulfonarnide is recovered by evaporation of the diethylether as a light yellow solid melting at 6470 C. which is recrystallized from benzene to a relatively pure product melting at 83-84" C. It is insoluble in cold Water but soluble in dilute hydrochloric acid and potassium hydroxide.

Analysis shows: Calculated for C H N O S: C, 46.1; H, 9.65; S, 14.3; N, 13.45 Found: C, 46.1; H, 9.4; S, 14.4; N, 13.3

' The preparation of beta-aminooctanesulfonamide may also be carried out employing an inert solvent. A suitable vessel is cooled to about 70 C. and charged with 230 parts (1 mole) of beta-chloro-octanesulfonyl fluoride, 230 parts of benzene and 85 parts (5 moles) of liquid ammonia. The vessel is sealed and heated to 90 C. (at this temperature the pressure is approximately 220 lbs. psi.) for 16 hours after which it is cooled to approximately 40 C., the residual pressure is released and the products of the reaction are diluted with additional benzene, heated and filtered. When the filtrate is concentrated and cooled to room temperature, crystals of crude beta-aminooctanesulfonamide are formed which are collected by filtration, washed with benzene and dried. The product beta-aminooctanesulfonamide has a melting point of about 83 C. and is identical to that obtained above.

It is further characterized by conversion to N-acetylbeta-aminooctanesulfonamide as follows:

To a mixture of 10.4 parts of the above beta-aminooctanesulfonamide and 4 parts of pyridine in about 35 parts of diethyl ether and about 50 parts of dioxane is added a solution of 4 parts of acetylchloride in about 20 parts of dioxane. Dilution of the reaction mixture with water and evaporation of the ether produces an insoluble white precipitate which is recrystallized from absolute ethanol to provide beta a-cetylaminooctanesulfonamide melting at about 138 C.

Analysis shows: Calculated for C H SO N C. 48.0;

4 H, 8.8; N, 11.2; S, 12.8. Found: C, 48.2;1-1, 8.5; N, 11.1; S, 12.4.

Example 2 This example illustrates the two step process and the isolation of the intermediate alkenesulfonyl fluoride.

A solution of 101 parts (1 mole) of triethylamine in about 700 parts of hexane in a glass vessel is heated to reflux and 230 parts (1 mole) of beta-chlorooctanesulfonyl fluoride are added at a rate to maintain the contents of the flask at reflux without external heating. After the addition is complete, refluxing is continued for V2 hour by means of external heat to complete the dehydrochlorination reaction. The reaction mixture is cooled and filtered to remove the precipitated triethylamine hydrochloride. This solid material is washed with hexane, and the filtrate and washes are combined. The l-octenesulfouyl fluoride produced in the reaction, which may be represented by the formula:

(C -H CH=CHSO F is isolated by evaporation of the volatile solvents from the combined filtrate and washes. It is a pale yellow liquid.

Amination is effected by heating about 10 parts of the intermediate l-octenesulfonyl fluoride and 5 parts of liq uid ammonia in a sealed vessel with agitation for about 16 hours at C. At the end of this reaction time the vessel is opened and the volatiles are evaporated. The residual white solid is worked up as in the first part of Example 1 to give a residue of ammonium fluoride and an ethereal solution from which white, solid beta-aminooctanesulfonamide is obtained on evaporation. After recrystallization from benzene the beta-aminooctanesulfonamide is found to melt at about 83 C. and is otherwise identical to the product of Example 1.

When the dehydrochlorination procedure of this exampie is repeated employing beta-chloro-isobutanesulfonyl fluoride, beta-chioro-butanesulfonyl fluoride and betachlorooctadecanesulfonyl chloride, the intermediate alkenesulfonyl fluorides obtained are respectively Z-methylprop-l-enesulfonyl fluoride, but-l-enesulfonyl fluoride and octadec-l-ene-sulfonyl fluoride. The intermediate alkenesulfonyl fluorides have the general formula:

R R'-(IJ=CHSO1F wherein R and R have their previous significance.

Example 3 A mixture of 20 parts (0.115 mole) of beta-chloro-- butanesulfonyl chloride, 20 parts (1.17 moles) of ammonia and 4 parts of benzene is sealed in a vessel as in Example 1 and is then heated at C. with agitation for 15 hours at the end of which time the vessel is cooled and opened. The semi-solid white residue comprises the hydrochloride of beta-aminobutanesulfonamide which is separated by solution in ethanol and evaporation of the filtered ethanolic extract to give a residue which is recrystallized from a benzene-ethanol mixture and then from an n-butanol-isopropanol-ethanol mixture. The resulting purified hydrochloride of beta-aminobutanesulfonamide melts at about to 187 C. It is soluble in water and ethanol and insoluble in non-polar solvents such as benzene, ether, etc.

Analysis: Calculated for C H SO N -HCl: C. 25.5; N, 14.9; S, 17.0. Found: C, 25.4; N, 14.9; S, 16.8.

The hydrochloride of beta-aminobutanesulfonamide is converted to the free aminobutanesulfonamide by addition of 5 percent sodium hydroxide to an aqueous solution of the hydrochloride to a pH of about 11. To recover the free beta-aminobutanesulfonamide, the basic aqueous;

solution is evaporated to dryness and the residue is slurriedi with absolute ethanol. After removal of the insolublesalts the filtrate is evaporated to provide yellowish oily betaaminobutanesulfonamide which solidifies. filqwly and;

5. then melts at about 60 to 65 C. Recrystallization from isopropyl alcohol provides crystalline beta-aminobutanesulfonamide melting at about 70 to 72.5 C.

Analysis.Calcuated for C H SO N C, 31.7; H, 7.9; N, 18.4. Found: C, 31.5; H, 7.7; N, 18.1.

Example 4 A mixture of 33.3 parts of beta-chlorooctadecanesulfonyl fluoride and 20 parts of anhydrous liquid ammonia is sealed in a vessel at about -60 C. and is then heated to 100 C. for approximately 16 hours with agitation in an autoclave. At the end of this time the autoclave is cooled and white solid beta-aminooctadecanesulfonamide, which maybe represented by the formula:

is recovered by the procedure hereinabove described. After crystallization from benzene this product melts at about 80 to 85 C.

Analysis.CalCulated for C13H40SO2N21 C, H, 11.5; N, 8.05. Found: C, 62.1; H, 11.1; N, 7.2.

Example 5 A mixture of 20 parts (0.115 mole) of freshly distilled beta-chloroisobutanesulfonyl fluoride, 8 parts of benzene and 17 parts (1.0 mole) of liquid ammonia sealed in a vessel according to the procedure of Example 1 is permitted to stand for approximately 16 hours at about 2 3 C. and the vessel and contents are then heated at about 95 C. with agitation for 120 hours. At the end of that time the vessel is cooled and opened. The hygroscopic solid residue comprises both free base and the hydrochloride. It is taken up in ethanol and filtered to remove salts. Evaporation of the ethanol from the filtrate leaves a clear, somewhat tacky material which is taken up in a mixture of butanol and ethanol from which crystals of beta-aminoisobutanesulfonamide hydrochloride separate slowly when the solvents are allowed to evaporate. These crystals are collected and recrystallized from 95 percent ethanol to furnish the hydrochloride of beta-aminoisobutanesulfonamide melting at about 189 C.

Analysis.Calculated for C H SO N CI: C, 25.5; H, 7.9; N,1'4.9. Found: C, 25.5; H, 7.0; N, 14.9.

The oily beta-aminoisobutanesulfonamide remaining in the mother liquors is recovered by evaporation of the solvents and is further characterized by conversion to N- benz-oyl-beta-aminoisobutanesulfonamide by heating a dioxane solution with benzoyl chloride in the presence of pyridine for 1 hour. This benzoylation mixture is diluted with water and extracted with ether. The ethereal solution is evaporated and the residue crystallized first from methanol and then from hot benzene containing 10 percent absolute ethanol. N-benzoyl-beta-aminoisobutanesulfonamide is obtained melting at about 181 C.

Analysis shows: Calculated for C H SO N C, 51.7; H, 6.1; N, 10.8. Found: C, 51.6; H, 6.3; N, 10.9.

When the procedures of these examples are repeated employing other beta-chloroalkanesulfonyl fluorides similar results are obtained. Thus, using the appropriate starting materials as set forth herein, there are prepared beta-aminopr-opanesulfonamide, beta-aminohexanesulfonamide, beta-aminododecanesulfonamide, beta-methyl-betaa-minobutanesulfonamide, and beta-ethyl-beta-aminobutanesulfonamide.

It is found in general that it is particularly diflicult to effect crystallization of lower members of this homologous series of laterally aminated alkanesulfonamides and these are often obtained as colorless to yellowish oils. In this form they are nevertheless useful as curing agents, as stated below. If desired, they are readily characterized by conversion to hydrochlorides or sulfates or to N-acyl derivatives as described above. Other simple conversions of both the amine and amide groups are also readily ef fected as will be obvious; however, for utility of these compounds it is usually preferred to retain both the amine and amide functions and these beta-aminoalkanesulfona-mides are useful in the curing of epoxy resins and formation of other polymers such as with urea and formaldehyde to produce a useful coating material.

For example, 10 parts of a liquid epoxy resin prepolymer (epoxide equivalent of about 190 to 200) is warmed and mixed with 2.5 parts of the beta-aminooctanesulfonamide of Example 1 and about 0.1 part of dimethylbenzylamine, and the fluid yellowish mixture is then heated at C. It gels in 5 minutes and is further heated at 130 C. for about 1.5 hours and at C. for '16 hours. The resultant cured resin is tough and stiff at room temperature and somewhat flexible at 150 C. Similar results are obtained when 4.3 parts of the beta-aminooctadecanesulfonamide of Example 4 is used in place of the beta aminooctanesulfonamide above.

What is claimed is:

1. The process for the preparation of fl-aminoalkanesulfonamides of the formula:

which comprises bringing together ammonia and a substituted sulfonyl fluoride of the formula:

wherein R is alkyl of 1 to 16 carbon atoms and R is a member of the group consisting of hydrogen and alkyl of 1 to 16 carbon atoms and maintaining them in a closed vessel at a temperature in the range of about 20 to about 200 C. under substantially autogenous pressure for a time suflicient to effect reaction.

2. The process for the preparation of fl-aminoalkanesulfonamides of the formula:

200 C. and under autogenous pressure for a time sufficient to effect reaction.

3. The process for the production of fi-aminoalkanesulfonamides of the formula:

which comprises bringing together ammonia and a substituted sulfonyl fluoride of the formula:

allk alk-(FOH;SOgF

wherein alk represents alkyl of up to 16 carbon atoms and maintaining them in a closed vessel at a temperature in the range of about 0 to about 200 C. and under autogenous pressure for a time suflicient to effect reaction.

(References on following page) References Cited by the Examiner UNITED FOREIGN PATENTS 8. OTHER REFERENCES STATES PATENTS Beilsteins Handbuch der Organischen Chemie, v01. 27,

Altamura 260 556 4th ed., page 3, system No. 4190, Verlag von Julius Tiers 260 556 Springer, Berlin, Germany (1937).

Tiers 260 556 X 5 Goldberg: J. Chem. Society (London), pp. 464-467 Tiers 260-556 (1945)- WALTER A. MODANCE, Primary Examiner.

Italy. IRVING MARCUS, Examiner. 

1. THE PROCESS FOR THE PREPARATION OF B-AMINOALKANESULFONAMIDES OF THE FORMULA:
 2. THE PROCESS FOR THE PREPARATION OF B-AMINOALKANESULFONAMIDES OF THE FORMULA: 